title: Changes in rabbit corneal innervation induced by the topical application of benzalkonium chloride.
abstract: OBJECTIVE
  To investigate the effect of benzalkonium chloride (BAK) on corneal nerves.
  
  
  METHODS
  Fifty-four adult New Zealand Albino rabbits were randomly divided into 3 groups. BAK at concentrations of 0.005%, 0.01%, or 0.02% was applied once daily to 1 eye of each rabbit for 9 days. The contralateral untreated eyes were used as controls. Corneal mechanical sensitivity, aqueous tear production, tear break-up time (BUT), fluorescein, and Rose Bengal staining scores were compared with those of control values on days 3, 6, and 9. Corneal whole mounts were immunostained with a specific antitubulin βIII antibody to label nerve fibers. Epithelial superficial nerve terminal, subbasal, and stromal nerve fiber densities were quantified. The structure of the central cornea was examined by means of in vivo confocal microscopy on day 9.
  
  
  RESULTS
  The topical application of BAK resulted in lower corneal sensitivity and higher Rose Bengal staining scores on day 3, whereas there were no significant changes in the BUT, Schirmer, and corneal fluorescein scores. Decreased nerve densities in superficial and subbasal layers were observed in BAK-treated eyes on days 3 and 6, respectively. The eyes treated with 0.02% BAK exhibited significantly reduced Schirmer scores, BUT, and stromal nerve fiber density, and increased fluorescein staining scores on day 9. Corneal superficial epithelial cell size was significantly larger in all BAK-treated eyes compared with that in control eyes.
  
  
  CONCLUSIONS
  The topical application of BAK can quickly cause corneal hypoesthesia without tear deficiency. Changes in corneal innervation significantly correlate with BAK-induced ocular surface changes.
authors.affiliation: Eye Institute and Affiliated Xiamen Eye Center, Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Vision Science, Xiamen, Fujian, China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Chen
authors.forename: Zhenhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jiaoyue
authors.initials: J
authors.lastname: Hu
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Juxin
authors.initials: J
authors.lastname: Pan
authors.forename: Nuo
authors.initials: N
authors.lastname: Dong
authors.forename: Zuguo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000287:Administration, Topical; D000704:Analysis of Variance; D000818:Animals; D001548:Benzalkonium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D003315:Cornea / Q000187:drug effects* / Q000294:innervation*; D003316:Corneal Diseases / Q000139:chemically induced* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D012395:Rose Bengal / Q000378:metabolism; D013666:Tears / Q000187:drug effects
chemical_list: D001548:Benzalkonium Compounds; D005452:Fluoresceins; D005456:Fluorescent Dyes; D012395:Rose Bengal